Department of Pathology and Medical Biology, Section of Immunoendocrinology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Grupo de Investigación Ciencia de los Materiales, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Medellín, Colombia.
Islets. 2022 Dec 31;14(1):164-183. doi: 10.1080/19382014.2022.2100191.
Transplantation of pancreatic islets is a promising approach to controlling glucose levels in type 1 diabetes mellitus (T1DM), but islet survival is still limited. To overcome this, islet co-culture with mesenchymal stromal cells (MSCs) together with safe immunosuppressive agents like squalene-gusperimus nanoparticles (Sq-GusNPs) may be applied. This could support islet survival and engraftment. Here, we studied how Sq-GusNPs and adipose-derived stem cells (ASCs) influence islets response under pro-inflammatory conditions. Through qRT-PCR, we studied the expression of specific genes at 24 hours in human and rat islets and ASCs in co-culture under indirect contact with or without treatment with Sq-GusNPs. We characterized how the response of islets and ASCs starts at molecular level before impaired viability or function is observed and how this response differs between species. Human islets and ASCs responses showed to be principally influenced by NF-κB activation, whereas rat islet and ASCs responses showed to be principally mediated by nitrosative stress. Rat islets showed tolerance to inflammatory conditions due to IL-1Ra secretion which was also observed in rat ASCs. Human islets induced the expression of cytokines and chemokines with pro-angiogenic, tissue repair, and anti-apoptotic properties in human ASCs under basal conditions. This expression was not inhibited by Sq-GusNPs. Our results showed a clear difference in the response elicited by human and rat islets and ASCs in front of an inflammatory stimulus and Sq-GusNPs. Our data support the use of ASCs and Sq-GusNP to facilitate engraftment of islets for T1DM treatment.
胰岛移植是控制 1 型糖尿病（T1DM）血糖水平的一种有前途的方法，但胰岛的存活率仍然有限。为了克服这一问题，可以将胰岛与间充质基质细胞（MSCs）共培养，并使用安全的免疫抑制剂，如角鲨烯-古司皮姆纳米颗粒（Sq-GusNPs）。这可能有助于支持胰岛的存活和植入。在这里，我们研究了 Sq-GusNPs 和脂肪来源的干细胞（ASCs）如何在炎症条件下影响胰岛的反应。通过 qRT-PCR，我们研究了人胰岛和大鼠胰岛与 ASC 在间接接触下共培养 24 小时时特定基因的表达，并在有无 Sq-GusNPs 处理的情况下进行了研究。我们描述了在观察到活力或功能受损之前，胰岛和 ASC 的反应如何从分子水平开始，以及这种反应在不同物种之间有何不同。人胰岛和 ASC 的反应主要受 NF-κB 激活的影响，而大鼠胰岛和 ASC 的反应主要受硝化应激的影响。大鼠胰岛由于 IL-1Ra 的分泌而对炎症条件具有耐受性，这种现象也在大鼠 ASC 中观察到。在基础条件下，人胰岛诱导人 ASC 表达细胞因子和趋化因子，具有促血管生成、组织修复和抗细胞凋亡的特性。这种表达不受 Sq-GusNPs 的抑制。我们的结果显示，人胰岛和 ASC 与大鼠胰岛和 ASC 对炎症刺激和 Sq-GusNPs 的反应存在明显差异。我们的数据支持使用 ASC 和 Sq-GusNP 促进 T1DM 治疗中胰岛的植入。
